The ultimate goal of the proposed research is to construct a kinetic model of metabolism in the normal rat liver as well as in the minimal deviation hepatomas 9618A and 7787. The comparison and exploration of these models may suggest which variables are critical in the transformation of the normal to the malignant metabolic state. Generalizations and predictions arising from an analysis of these models may then be validated or refuted by investigations on other hepatomas which vary in growth rate. Initial investigations will be concentrated in the area of glycogen metabolism, because of its importance to liver function and because of the extensive information available in the literature for normal liver. As data become available, the model will be expanded and related to other general (protein, energy, etc.) and specialized (e.g., urea and albumin synthesis) areas of metabolism. A closely related objective is an investigation of the control of enzyme activity and levels in vivo in minimal deviation tumors as compared to normal liver. The regulation and turnover of several enzymes critical to the control of glycogen metabolism will be examined, including soluble glucokinase and glycogen phosphorylase. The purification and characterization of these enzymes will also yield data necessary for the construction of the proposed kinetic models. The exploration of these models will in turn reveal other enzymes in positions of critical importance to metabolic regulation.